Antimicrobial Drug Use and Resistance in Europe

Routine surveillance data indicate a relation between use and resistance and support interventions designed to reduce antimicrobial consumption at a national level in Europe

Antimicrobial resistance in invasive strains of Escherichia coli from southern and eastern Mediterranean laboratories

From January 2003 to December 2005, 5091 susceptibility test results from invasive isolates of Escherichia coli, collected from blood cultures and cerebrospinal fluid routinely processed within 58 participating laboratories, were investigated. These laboratories in turn serviced 64 hospitals in Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey. The median proportion of resistance to third-generation cephalosporins for the duration of the project was 18.9% (interquartile range (IQR): 12.5–30.8%), and for fluoroquinolones 21.0% (IQR: 7.7–32.6%). A substantial proportion of strains reported by laboratories in countries east of the Mediterranean exhibited evidence of multiresistance, the highest proportion being from Egypt (31%). There is clearly a need for further investigation of potential causes of the significant resistance identified, as well as for strengthening of national and international surveillance initiatives within this region.‘peer-reviewe

Antimicrobial drug use and resistance in Europe

Our study confronts the use of antimicrobial agents in ambulatory care with the resistance trends of 2 major pathogens, Streptococcus pneumoniae and Escherichia coli, in 21 European countries in 2000–2005 and explores whether the notion that antimicrobial drug use determines resistance can be supported by surveillance data at national aggregation levels. The data obtained from the European Surveillance of Antimicrobial Consumption and the European Antimicrobial Resistance Surveillance System suggest that variation of consumption coincides with the occurrence of resistance at the country level. Linear regression analysis showed that the association between antimicrobial drug use and resistance was specific and robust for 2 of 3 compound pathogen combinations, stable over time, but not sensitive enough to explain all of the observed variations. Ecologic studies based on routine surveillance data indicate a relation between use and resistance and support interventions designed to reduce antimicrobial drug consumption at a national level in Europe.peer-reviewe

Large-scale gene-centric analysis identifies novel variants for coronary artery disease

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ~2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p&lt;10-33; LPA:p&lt;10-19; 1p13.3:p&lt;10-17) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p&lt;5×10-7). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ~4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.</p

Heart failure following STEMI: a contemporary cohort study of incidence and prognostic factors

The aim of the current study was to determine the contemporary incidence, risk factors and prognosis of heart failure (HF) after ST-elevation myocardial infarction (STEMI). We used the Arrhythmia Genetics in the Netherlands observational cohort study to identify patients with a first STEMI from 2001 onwards (n=1459). HF during follow-up was defined as hospitalisation for HF or an outpatient clinic visit for HF. Cox regression was performed to estimate the relationship between baseline covariates and the onset of HF. Follow-up was completed for 1360 (93.2%) patients with an overall median follow-up time of 6.7 years, 1232 (90.6%) of these patients had undergone primary percutaneous coronary intervention (PCI). A total of 85 patients (6.3%) developed HF during follow-up. HF cases were significantly older at their index MI (59.9 vs 57.2 years, P <0.001) and more commonly had a history of atrial fibrillation (6.1% vs 1.4%, P=0.001) than controls without HF. The crude incidence rate of HF after STEMI was 9.7 (95% CI 7.7 to 11.8) per 1000 person-years. In multivariable analysis, peak creatine kinase MB (CK-MB) levels (HR 1.11 per 100 U/L (95% CI 1.11 to 1.22)) and a left anterior descending artery (LAD) culprit lesion (HR 2.88 (95% CI 1.53 to 5.40)) were risk factors associated with HF. We found a relatively low long-term contemporary incidence of HF after a first STEMI in the current PCI era in comparison with other reports. Higher CK-MB levels and a LAD culprit lesion at index STEMI were important risk factors for the development of HF after STEMI. NCT03007199; Result

SNPs identified as modulators of ECG traits in the general population do not markedly affect ECG traits during acute myocardial infarction nor ventricular fibrillation risk in this condition.

BackgroundVentricular fibrillation (VF) in the setting of acute ST elevation myocardial infarction (STEMI) is a leading cause of mortality. Although the risk of VF has a genetic component, the underlying genetic factors are largely unknown. Since heart rate and ECG intervals of conduction and repolarization during acute STEMI differ between patients who do and patients who do not develop VF, we investigated whether SNPs known to modulate these ECG indices in the general population also impact on the respective ECG indices during STEMI and on the risk of VF.Methods and resultsThe study population consisted of participants of the Arrhythmia Genetics in the NEtherlandS (AGNES) study, which enrols patients with a first STEMI that develop VF (cases) and patients that do not develop VF (controls). SNPs known to impact on RR interval, PR interval, QRS duration or QTc interval in the general population were tested for effects on the respective STEMI ECG indices (stage 1). Only those showing a (suggestive) significant association were tested for association with VF (stage 2). On average, VF cases had a shorter RR and a longer QTc interval compared to non-VF controls. Eight SNPs showed a trend for association with the respective STEMI ECG indices. Of these, three were also suggestively associated with VF.ConclusionsRR interval and ECG indices of conduction and repolarization during acute STEMI differ between patients who develop VF and patients who do not. Although the effects of the SNPs on ECG indices during an acute STEMI seem to be similar in magnitude and direction as those found in the general population, the effects, at least in isolation, are too small to explain the differences in ECGs between cases and controls and to determine risk of VF

Driving multisectoral antimicrobial resistance action in South America: Lessons learned from implementing an enhanced tripartite AMR country self-assessment tool

As part of an innovative Tripartite-EU collaboration Project that supports seven South American countries, a Landscape Analysis Tool (LAT) was developed and implemented to collect data to complement the Tripartite AMR Country Self-Assessment Survey (TrACSS) process. The LAT enables collection of broader and deeper information to guide development of priority One Health activities, and strengthen national action plans to combat antimicrobial resistance. The Project developed the tool, trained a consultant pool in its use, and implemented it in conjunction with multi-sectoral country teams. The main results were seven priority-informed country workplans that proposed specific activities in line with the Strategic Objectives of each country's national action plan. LAT implementation clearly showed that the tool is a strong complement to the TrACSS process and that there can be considerable benefit to the process of collecting additional data layers, especially to strengthen country ownership of AMR-related information and solidifying multisectoral engagement. Countries elsewhere might consider implementing this complementary tool – either once to establish a baseline – or periodically to gain a better ongoing understanding of the situation on the ground

Heart failure following STEMI : a contemporary cohort study of incidence and prognostic factors

Objective: The aim of the current study was to determine the contemporary incidence, risk factors and prognosis of heart failure (HF) after ST-elevation myocardial infarction (STEMI). Methods: We used the Arrhythmia Genetics in the Netherlands observational cohort study to identify patients with a first STEMI from 2001 onwards (n=1459). HF during follow-up was defined as hospitalisation for HF or an outpatient clinic visit for HF. Cox regression was performed to estimate the relationship between baseline covariates and the onset of HF. Results: Follow-up was completed for 1360 (93.2%) patients with an overall median follow-up time of 6.7 years, 1232 (90.6%) of these patients had undergone primary percutaneous coronary intervention (PCI). A total of 85 patients (6.3%) developed HF during follow-up. HF cases were significantly older at their index MI (59.9 vs 57.2 years, P<0.001) and more commonly had a history of atrial fibrillation (6.1% vs 1.4%, P=0.001) than controls without HF. The crude incidence rate of HF after STEMI was 9.7 (95% CI 7.7 to 11.8) per 1000 person-years. In multivariable analysis, peak creatine kinase MB (CK-MB) levels (HR 1.11 per 100 U/L (95% CI 1.11 to 1.22)) and a left anterior descending artery (LAD) culprit lesion (HR 2.88 (95% CI 1.53 to 5.40)) were risk factors associated with HF. Conclusions: We found a relatively low long-term contemporary incidence of HF after a first STEMI in the current PCI era in comparison with other reports. Higher CK-MB levels and a LAD culprit lesion at index STEMI were important risk factors for the development of HF after STEMI. Trial registration number: NCT03007199; Results